rs523611

Variant names:

• chr10-77290690-G-C
• rs523611
• NM_001161352.2:c.541-39434C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-77290690-G-C
• chr10-77290690-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.541-39434C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,940 control chromosomes in the GnomAD database, including 18,050 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (18050 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 3 publications found

Genes affected

KCNMA1 (HGNC:6284): (potassium calcium-activated channel subfamily M alpha 1) This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]

KCNMA1 Gene-Disease associations (from GenCC):

• generalized epilepsy-paroxysmal dyskinesia syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• Liang-Wang syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• cerebellar atrophy, developmental delay, and seizures

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.541-39434C>G		intron_variant	Intron 2 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.541-39434C>G		intron_variant	Intron 2 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71222 AN: 151822 Hom.: 18042 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.461

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.469 AC: 71261 AN: 151940 Hom.: 18050 Cov.: 32 AF XY: 0.463 AC XY: 34422 AN XY: 74272

African (AFR) AF: 0.328 AC: 13606 AN: 41440

American (AMR) AF: 0.470 AC: 7184 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1723 AN: 3470

East Asian (EAS) AF: 0.151 AC: 781 AN: 5168

South Asian (SAS) AF: 0.296 AC: 1424 AN: 4806

European-Finnish (FIN) AF: 0.535 AC: 5645 AN: 10542

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 38982 AN: 67918

Other (OTH) AF: 0.462 AC: 977 AN: 2114

Alfa AF: 0.398 Hom.: 1202

Bravo AF: 0.458

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs523611; hg19: chr10-79050448;